Combinatorial and High-Throughput Screening of Materials ...

ACS Combinatorial Science
REVIEW
Figure 44. Polysebacic acid and poly[1,6-bis(p-carboxyphenoxy) hexane] based monomers used in biocopolymers.
Figure 46. Discrete and continuous experimental phase diagrams used
in poly(CPH)/poly(SA) blends. 449
Figure 45. Schematic of photolithographic design of discrete thiolene
well substrates. 449
technologies have been extensively used by various research
groups to accelerate discovery of these important materials.
Biodegradable polymers for drug delivery have been the focus of
engineered materials used for the delivery of drug molecules or
genes but also used as encapsulant for gene therapy. In 2008,
446 448
Meredith has reviewed recent advances in the past 10 years.
Recently, Thortensen et al. developed biodegradable polymers
bearing a poly[1,6-bis(p-carboxyphenoxy) hexane] (CPH) and poly-
[sebacic anhydride] (SA) backbone and evaluated them as vehicles
for drug delivery (see Figure 44). 449 Libraries of those polymers were
made by using a combination of solution-based gradient deposition
and rapid prototyping. 450 452 These materials have been the focus of
studies looking at the effect of blend miscibility on the biodegradability
of the material using CHT techniques. The discrete libraries were
made on a Si wafer via the thiolene chemistry. The fabrication of
discrete well plates was accomplished by photolithography. The basic
idea is to form wall-like structures by selectively polymerizing areas of
a thiolene-based resin by means of a collimated UV source and
discriminating mask as shown in Figure 45.
On the other hand, the continuous libraries were prepared by
using a modified procedure to the one published by Meredith
et al. in a 3 step standard workflow (gradient mixing, gradient
deposition, and film spreading (see Figure 45 and 46) using
custom-made automation platforms. 453
Blend compositions were characterized by high throughput
transmission Fourier transform infrared (FTIR). The phase
diagrams of CPH/SA polymers, the effect of blend composition
and annealing temperature on the miscibility of the blend were
studied to determine blend miscibility, which is a great indication
for polymer viability and stability. The gradient library was
further examined with optical microscopy and Atomic Force
Microscopy for surface morphology and roughness but also to
locate the miscibility phase boundary marked by differential
microstructure-induced opacity fluctuations (cloud points). A
good correlation was found between results obtained by theoretical
phase diagrams determination and with surface analysis
obtained with these blends. 454 Evaluation of those materials of
similar chemical composition made by CHT was carried out by
the same research group and the effect of polymer chemistry and
device geometry on the in vitro activation of murine dendritic
cells was determined. 105
Petersen et al. described the development of polyanhydrides
and the subsequent use for materials enabling controlled drug
release, drug stability, or immune regulation (adjuvant effect).
Understanding the induction of immunomodulatory mechanisms
of this polymer system is important for the design and
development of efficacious vaccines and tissue compatible multicomponent
implantable devices. In light of this, combinatorial
libraries of polyanhydride materials of various sebacic acid (SA)
and 1,6 bis(p-carboxyphenoxy)hexane (CPH) were made as
films and/or nanospheres and tested rapidly in in vitro tests.
Discrete, combinatorial film libraries, linearly varying in copolymer
composition of the CPH:SA system, were automatically
characterized with FTIR. 105
The polyanhydride array of biomaterials was tested in cell
surface marker expression and cytokine production. Figure 47
showed the interleukine IL-6 and IL12p40 by C57BL/6 DCs
results with the multiplexed CPH:SA libraries. The CPH:SA
polymer film system provided a gentle, biocompatible environment
necessary for multicomponent implants. In contrast, the
CPH:SA nanosphere system provided an adjuvant effect by
619 dx.doi.org/10.1021/co200007w |ACS Comb. Sci. 2011, 13, 579–633